Abstract
Primary lymphedema of the upper extremity is rare and often is associated with syndromic or generalized lymphedema. The purpose of the study was to identify novel causes for primary lymphedema of the arm. A 17-year-old healthy male with right upper extremity swelling since infancy was confirmed to have lymphedema by lymphoscintigraphy. He subsequently developed right leg disease in adolescence and his mother had lower extremity lymphedema as well. Whole-exome sequencing of genomic DNA from the subject identified a frameshift deletion resulting in a premature stop codon in exon 3 of the CELSR1 gene hg19: chr22:46,835,160_46,835,166del (c.4326_4332del; p.T1443Gfs*14). The variant was confirmed in the patient and his mother by Sanger sequencing. A novel variant in CELSR1 causes nonsyndromic upper extremity lymphedema; other variants in this gene previously have been associated with lower extremity disease.